This page has only limited features, please log in for full access.

Unclaimed
Chao Zhang
CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China

Honors and Awards

The user has no records in this section


Career Timeline

The user has no records in this section.


Short Biography

The user biography is not available.
Following
Followers
Co Authors
The list of users this user is following is empty.
Following: 0 users

Feed

Journal article
Published: 18 August 2021 in Cell Discovery
Reads 0
Downloads 0

Massive production of efficacious SARS-CoV-2 vaccines is essential for controlling the ongoing COVID-19 pandemic. We report here the preclinical development of yeast-produced receptor-binding domain (RBD)-based recombinant protein SARS-CoV-2 vaccines. We found that monomeric RBD of SARS-CoV-2 could be efficiently produced as a secreted protein from transformed Pichia pastoris (P. pastoris) yeast. Yeast-derived RBD-monomer possessed functional conformation and was able to elicit protective level of neutralizing antibodies in mice. We further designed and expressed a genetically linked dimeric RBD protein in yeast. The engineered dimeric RBD was more potent than the monomeric RBD in inducing long-lasting neutralizing antibodies. Mice immunized with either monomeric RBD or dimeric RBD were effectively protected from live SARS-CoV-2 virus challenge even at 18 weeks after the last vaccine dose. Importantly, we found that the antisera raised against the RBD of a single SARS-CoV-2 prototype strain could effectively neutralize the two predominant circulating variants B.1.1.7 and B.1.351, implying broad-spectrum protective potential of the RBD-based vaccines. Our data demonstrate that yeast-derived RBD-based recombinant SARS-CoV-2 vaccines are feasible and efficacious, opening up a new avenue for rapid and cost-effective production of SARS-CoV-2 vaccines to achieve global immunization.

ACS Style

Jinkai Zang; Yuanfei Zhu; Yu Zhou; Chenjian Gu; Yufang Yi; Shuxia Wang; Shiqi Xu; Gaowei Hu; Shujuan Du; Yannan Yin; Yalei Wang; Yong Yang; Xueyang Zhang; Haikun Wang; Feifei Yin; Chao Zhang; Qiang Deng; Youhua Xie; Zhong Huang. Yeast-produced RBD-based recombinant protein vaccines elicit broadly neutralizing antibodies and durable protective immunity against SARS-CoV-2 infection. Cell Discovery 2021, 7, 1 .

AMA Style

Jinkai Zang, Yuanfei Zhu, Yu Zhou, Chenjian Gu, Yufang Yi, Shuxia Wang, Shiqi Xu, Gaowei Hu, Shujuan Du, Yannan Yin, Yalei Wang, Yong Yang, Xueyang Zhang, Haikun Wang, Feifei Yin, Chao Zhang, Qiang Deng, Youhua Xie, Zhong Huang. Yeast-produced RBD-based recombinant protein vaccines elicit broadly neutralizing antibodies and durable protective immunity against SARS-CoV-2 infection. Cell Discovery. 2021; 7 ():1.

Chicago/Turabian Style

Jinkai Zang; Yuanfei Zhu; Yu Zhou; Chenjian Gu; Yufang Yi; Shuxia Wang; Shiqi Xu; Gaowei Hu; Shujuan Du; Yannan Yin; Yalei Wang; Yong Yang; Xueyang Zhang; Haikun Wang; Feifei Yin; Chao Zhang; Qiang Deng; Youhua Xie; Zhong Huang. 2021. "Yeast-produced RBD-based recombinant protein vaccines elicit broadly neutralizing antibodies and durable protective immunity against SARS-CoV-2 infection." Cell Discovery 7, no. : 1.

Communication
Published: 22 July 2021 in Viruses
Reads 0
Downloads 0

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most of the currently approved SARS-CoV-2 vaccines use the prototype strain-derived spike (S) protein or its receptor-binding domain (RBD) as the vaccine antigen. The emergence of several novel SARS-CoV-2 variants has raised concerns about potential immune escape. In this study, we performed an immunogenicity comparison of prototype strain-derived RBD, S1, and S ectodomain trimer (S-trimer) antigens and evaluated their induction of neutralizing antibodies against three circulating SARS-CoV-2 variants, including B.1.1.7, B.1.351, and B.1.617.1. We found that, at the same antigen dose, the RBD and S-trimer vaccines were more potent than the S1 vaccine in eliciting long-lasting, high-titer broadly neutralizing antibodies in mice. The RBD immune sera remained highly effective against the B.1.1.7, B.1.351, and B.1.617.1 variants despite the corresponding neutralizing titers decreasing by 1.2-, 2.8-, and 3.5-fold relative to that against the wild-type strain. Significantly, the S-trimer immune sera exhibited comparable neutralization potency (less than twofold variation in neutralizing GMTs) towards the prototype strain and all three variants tested. These findings provide valuable information for further development of recombinant protein-based SARS-CoV-2 vaccines and support the continued use of currently approved SARS-CoV-2 vaccines in the regions/countries where variant viruses circulate.

ACS Style

Yong Yang; Jinkai Zang; Shiqi Xu; Xueyang Zhang; Sule Yuan; Haikun Wang; Dimitri Lavillette; Chao Zhang; Zhong Huang. Elicitation of Broadly Neutralizing Antibodies against B.1.1.7, B.1.351, and B.1.617.1 SARS-CoV-2 Variants by Three Prototype Strain-Derived Recombinant Protein Vaccines. Viruses 2021, 13, 1421 .

AMA Style

Yong Yang, Jinkai Zang, Shiqi Xu, Xueyang Zhang, Sule Yuan, Haikun Wang, Dimitri Lavillette, Chao Zhang, Zhong Huang. Elicitation of Broadly Neutralizing Antibodies against B.1.1.7, B.1.351, and B.1.617.1 SARS-CoV-2 Variants by Three Prototype Strain-Derived Recombinant Protein Vaccines. Viruses. 2021; 13 (8):1421.

Chicago/Turabian Style

Yong Yang; Jinkai Zang; Shiqi Xu; Xueyang Zhang; Sule Yuan; Haikun Wang; Dimitri Lavillette; Chao Zhang; Zhong Huang. 2021. "Elicitation of Broadly Neutralizing Antibodies against B.1.1.7, B.1.351, and B.1.617.1 SARS-CoV-2 Variants by Three Prototype Strain-Derived Recombinant Protein Vaccines." Viruses 13, no. 8: 1421.

Journal article
Published: 18 May 2021 in Nature Communications
Reads 0
Downloads 0

Enterovirus D68 (EV-D68) is an emerging pathogen associated with respiratory diseases and/or acute flaccid myelitis. Here, two MAbs, 2H12 and 8F12, raised against EV-D68 virus-like particle (VLP), show distinct preference in binding VLP and virion and in neutralizing different EV-D68 strains. A combination of 2H12 and 8F12 exhibits balanced and potent neutralization effects and confers broader protection in mice than single MAbs when given at onset of symptoms. Cryo-EM structures of EV-D68 virion complexed with 2H12 or 8F12 show that both antibodies bind to the canyon region of the virion, creating steric hindrance for sialic acid receptor binding. Additionally, 2H12 binding can impair virion integrity and trigger premature viral uncoating. We also capture an uncoating intermediate induced by 2H12 binding, not previously described for picornaviruses. Our study elucidates the structural basis and neutralizing mechanisms of the 2H12 and 8F12 MAbs and supports further development of the 2H12/8F12 cocktail as a broad-spectrum therapeutic agent against EV-D68 infections in humans.

ACS Style

Chao Zhang; Cong Xu; Wenlong Dai; Yifan Wang; Zhi Liu; Xueyang Zhang; Xuesong Wang; Haikun Wang; Sitang Gong; Yao Cong; Zhong Huang. Functional and structural characterization of a two-MAb cocktail for delayed treatment of enterovirus D68 infections. Nature Communications 2021, 12, 1 -16.

AMA Style

Chao Zhang, Cong Xu, Wenlong Dai, Yifan Wang, Zhi Liu, Xueyang Zhang, Xuesong Wang, Haikun Wang, Sitang Gong, Yao Cong, Zhong Huang. Functional and structural characterization of a two-MAb cocktail for delayed treatment of enterovirus D68 infections. Nature Communications. 2021; 12 (1):1-16.

Chicago/Turabian Style

Chao Zhang; Cong Xu; Wenlong Dai; Yifan Wang; Zhi Liu; Xueyang Zhang; Xuesong Wang; Haikun Wang; Sitang Gong; Yao Cong; Zhong Huang. 2021. "Functional and structural characterization of a two-MAb cocktail for delayed treatment of enterovirus D68 infections." Nature Communications 12, no. 1: 1-16.

Research article
Published: 01 January 2021 in Emerging Microbes & Infections
Reads 0
Downloads 0

Human noroviruses are the dominant causative agent of acute viral gastroenteritis worldwide. During the winter of 2014-2015, genotype GII.17 cluster IIIb strains emerged as the leading cause of norovirus infection in Asia and later spread to other parts of the world. It is speculated that mutation at blockade epitopes may have resulted in virus escape from herd immunity, leading to the emergence of GII.17 cluster IIIb variants. Here we identify a GII.17 cluster IIIb-specific blockade epitope by monoclonal antibody (mAb)-based epitope mapping. Four mAbs (designated as M1 to M4) were generated from mice immunized with virus-like particle (VLP) of a GII.17 cluster IIIb strain. Among them, M1 and M3 reacted specifically with the cluster IIIb VLP but not with the VLPs from clusters II or IIIa. Moreover, M1 and M3 dose-dependently blocked cluster IIIb VLP binding with its ligand, histo-blood group antigens (HBGAs). Epitope mapping revealed that M1 and M3 recognized the same highly exposed epitope consisting of residues 293-296 and 299 in the capsid protein VP1. Sequence alignment showed that the M1/M3 epitope sequence is highly variable among different GII.17 clusters whereas it is identical for cluster IIIIb strains. These data define a dominant blockade epitope of GII.17 norovirus and provide evidence that blockade epitope evolution contributes to the emergence of GII.17 cluster IIIb strains.

ACS Style

Yufang Yi; Xiaoli Wang; Shuxia Wang; Pei Xiong; Qingwei Liu; Chao Zhang; Feifei Yin; Zhong Huang. Identification of a blockade epitope of human norovirus GII.17. Emerging Microbes & Infections 2021, 10, 954 -963.

AMA Style

Yufang Yi, Xiaoli Wang, Shuxia Wang, Pei Xiong, Qingwei Liu, Chao Zhang, Feifei Yin, Zhong Huang. Identification of a blockade epitope of human norovirus GII.17. Emerging Microbes & Infections. 2021; 10 (1):954-963.

Chicago/Turabian Style

Yufang Yi; Xiaoli Wang; Shuxia Wang; Pei Xiong; Qingwei Liu; Chao Zhang; Feifei Yin; Zhong Huang. 2021. "Identification of a blockade epitope of human norovirus GII.17." Emerging Microbes & Infections 10, no. 1: 954-963.

Research article
Published: 04 December 2020 in Science Advances
Reads 0
Downloads 0

The recent outbreaks of SARS-CoV-2 pose a global health emergency. The SARS-CoV-2 trimeric spike (S) glycoprotein interacts with the human ACE2 receptor to mediate viral entry into host cells. We report the cryo-EM structures of a tightly closed SARS-CoV-2 S trimer with packed fusion peptide and an ACE2-bound S trimer at 2.7- and 3.8-Å resolution, respectively. Accompanying ACE2 binding to the up receptor-binding domain (RBD), the associated ACE2-RBD exhibits continuous swing motions. Notably, the SARS-CoV-2 S trimer appears much more sensitive to the ACE2 receptor than the SARS-CoV S trimer regarding receptor-triggered transformation from the closed prefusion state to the fusion-prone open state, potentially contributing to the superior infectivity of SARS-CoV-2. We defined the RBD T470-T478 loop and Y505 as viral determinants for specific recognition of SARS-CoV-2 RBD by ACE2. Our findings depict the mechanism of ACE2-induced S trimer conformational transitions from the ground prefusion state toward the postfusion state, facilitating development of anti–SARS-CoV-2 vaccines and therapeutics.

ACS Style

Cong Xu; Yanxing Wang; Caixuan Liu; Chao Zhang; Wenyu Han; Xiaoyu Hong; Yifan Wang; Qin Hong; Shutian Wang; Qiaoyu Zhao; Yalei Wang; Yong Yang; Kaijian Chen; Wei Zheng; Liangliang Kong; Fangfang Wang; Qinyu Zuo; Zhong Huang; Yao Cong. Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM. Science Advances 2020, 7, eabe5575 .

AMA Style

Cong Xu, Yanxing Wang, Caixuan Liu, Chao Zhang, Wenyu Han, Xiaoyu Hong, Yifan Wang, Qin Hong, Shutian Wang, Qiaoyu Zhao, Yalei Wang, Yong Yang, Kaijian Chen, Wei Zheng, Liangliang Kong, Fangfang Wang, Qinyu Zuo, Zhong Huang, Yao Cong. Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM. Science Advances. 2020; 7 (1):eabe5575.

Chicago/Turabian Style

Cong Xu; Yanxing Wang; Caixuan Liu; Chao Zhang; Wenyu Han; Xiaoyu Hong; Yifan Wang; Qin Hong; Shutian Wang; Qiaoyu Zhao; Yalei Wang; Yong Yang; Kaijian Chen; Wei Zheng; Liangliang Kong; Fangfang Wang; Qinyu Zuo; Zhong Huang; Yao Cong. 2020. "Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM." Science Advances 7, no. 1: eabe5575.

Journal article
Published: 01 December 2019 in Plants
Reads 0
Downloads 0

Enterovirus 71 (EV71) is the main causative agent of severe hand-foot-mouth disease. EV71 affects countries mainly in the Asia-Pacific region, which makes it unattractive for pharmaceutical companies to develop drugs or vaccine to combat EV71 infection. However, development of these drugs and vaccines is vital to protect younger generations. This study aims to develop a specific monoclonal antibody (mAb) to EV71 using a plant platform, which is a cost-effective and scalable production technology. A previous report showed that D5, a murine anti-EV71 mAb, binds to VP1 protein of EV71, potently neutralizes EV71 in vitro, and effectively protects mice against EV71 infection. Herein, plant-produced chimeric D5 (cD5) mAb, variable regions of murine D5 antibody linked with constant regions of human IgG1, was transiently expressed in Nicotiana benthamiana using geminiviral vectors. The antibody was expressed at high levels within six days of infiltration. Plant-produced cD5 retained its in vitro high-affinity binding and neutralizing activity against EV71. Furthermore, a single dose (10 µg/g body weight) of plant-produced cD5 mAb offered 100% protection against infection in mice after a lethal EV71 challenge. Therefore, our results showed that plant-produced anti-EV71 mAb is an effective, safe, and affordable therapeutic option against EV71 infection.

ACS Style

Kaewta Rattanapisit; Zhang Chao; Konlavat Siriwattananon; Zhong Huang; Waranyoo Phoolcharoen. Plant-Produced Anti-Enterovirus 71 (EV71) Monoclonal Antibody Efficiently Protects Mice Against EV71 Infection. Plants 2019, 8, 560 .

AMA Style

Kaewta Rattanapisit, Zhang Chao, Konlavat Siriwattananon, Zhong Huang, Waranyoo Phoolcharoen. Plant-Produced Anti-Enterovirus 71 (EV71) Monoclonal Antibody Efficiently Protects Mice Against EV71 Infection. Plants. 2019; 8 (12):560.

Chicago/Turabian Style

Kaewta Rattanapisit; Zhang Chao; Konlavat Siriwattananon; Zhong Huang; Waranyoo Phoolcharoen. 2019. "Plant-Produced Anti-Enterovirus 71 (EV71) Monoclonal Antibody Efficiently Protects Mice Against EV71 Infection." Plants 8, no. 12: 560.

Journal article
Published: 30 January 2018 in Viruses
Reads 0
Downloads 0

In recent years, enterovirus D68 (EVD68) has been reported increasingly to be associated with severe respiratory tract infections and acute flaccid myelitis (AFM) in children all over the world. Yet, no effective vaccines or antiviral drugs are currently available for EVD68. Although several experimental animal models have been developed, immunogenicity and protective efficacy of inactivated EVD68 vaccines has not been fully evaluated. To promote the development of vaccines, we established an Institute of Cancer Research (ICR) suckling mouse model of EVD68 infection in this study. The results showed that ICR neonatal mice up to about nine days of age were susceptible to infection with EVD68 clinical strain US/MO/14-18947 by intraperitoneal injection. The infected mice exhibited progressive limb paralysis prior to death and the mortality of mice was age- and virus dose-dependent. Tissue viral load analysis showed that limb muscle and spinal cord were the major sites of viral replication. Moreover, histopathologic examination revealed the severe necrosis of the limb and juxtaspinal muscles, suggesting that US/MO/14-18947 has a strong tropism toward muscle tissues. Additionally, β-propiolactone-inactivated EVD68 vaccine showed high purity and quality and induced robust EVD68-specific neutralizing antibody responses in adult mice. Importantly, results from both antisera transfer and maternal immunization experiments clearly showed that inactivated EVD68 vaccine was able to protect against lethal viral infection in the mouse model. In short, these results demonstrate the successful establishment of the mouse model of EVD68 infection for evaluating candidate vaccines against EVD68 and also provide important information for the development of inactivated virus-based EVD68 vaccines.

ACS Style

Chao Zhang; Xueyang Zhang; Wenlong Dai; Qingwei Liu; Pei Xiong; Shuxia Wang; Lanlan Geng; Sitang Gong; Zhong Huang. A Mouse Model of Enterovirus D68 Infection for Assessment of the Efficacy of Inactivated Vaccine. Viruses 2018, 10, 58 .

AMA Style

Chao Zhang, Xueyang Zhang, Wenlong Dai, Qingwei Liu, Pei Xiong, Shuxia Wang, Lanlan Geng, Sitang Gong, Zhong Huang. A Mouse Model of Enterovirus D68 Infection for Assessment of the Efficacy of Inactivated Vaccine. Viruses. 2018; 10 (2):58.

Chicago/Turabian Style

Chao Zhang; Xueyang Zhang; Wenlong Dai; Qingwei Liu; Pei Xiong; Shuxia Wang; Lanlan Geng; Sitang Gong; Zhong Huang. 2018. "A Mouse Model of Enterovirus D68 Infection for Assessment of the Efficacy of Inactivated Vaccine." Viruses 10, no. 2: 58.

Journal article
Published: 05 January 2018 in Viruses
Reads 0
Downloads 0

Noroviruses (NoVs) are the main pathogens responsible for sporadic and epidemic nonbacterial gastroenteritis, causing an estimated 219,000 deaths annually worldwide. There is no commercially available vaccine for NoVs, due partly to the difficulty in establishing NoV cell culture models. The histo-blood group antigen (HBGA) blocking assay is used extensively to assess the protective potential of candidate vaccine-elicited antibodies, but there is still no widely used cellular evaluation model. In this study, we have established a cell line-based NoV vaccine evaluation model through the construction of human α1,2-fucosyltransferase 2-overexpressing 293T (293T-FUT2) cell lines. The 293T-FUT2 cells stably expressed H type 2 and Lewis y antigens. Virus-like particles (VLPs) of the NoV prototype strain genogroup I.1 (GI.1) and the predominant strains GII.4 and GII.17 could attach to the cell line efficiently in a dose-dependent manner. Importantly, antisera against these NoV VLPs could inhibit the attachment of the VLPs, where the inhibitory effects measured by the attachment inhibition assay correlated significantly with the antibody levels determined by the HBGA blocking assay. Collectively, our attachment inhibition assay could serve as a surrogate neutralization assay for the evaluation of NoV vaccines at the cellular level.

ACS Style

Xiaoli Wang; Shuxia Wang; Chao Zhang; Yu Zhou; Pei Xiong; Qingwei Liu; Zhong Huang. Development of a Surrogate Neutralization Assay for Norovirus Vaccine Evaluation at the Cellular Level. Viruses 2018, 10, 27 .

AMA Style

Xiaoli Wang, Shuxia Wang, Chao Zhang, Yu Zhou, Pei Xiong, Qingwei Liu, Zhong Huang. Development of a Surrogate Neutralization Assay for Norovirus Vaccine Evaluation at the Cellular Level. Viruses. 2018; 10 (1):27.

Chicago/Turabian Style

Xiaoli Wang; Shuxia Wang; Chao Zhang; Yu Zhou; Pei Xiong; Qingwei Liu; Zhong Huang. 2018. "Development of a Surrogate Neutralization Assay for Norovirus Vaccine Evaluation at the Cellular Level." Viruses 10, no. 1: 27.